How Nature’s Ozempic may also help in the fight against Alzheimer's Disease

Rarely do we find supplements that are only beneficial to one thing in our body. Such is the case with berberine, a dietary supplement that has grown in popularity over the years for it’s weight loss properties and has even been dubbed “Nature’s Ozempic” due to its GLP-1 secreting abilities (Li et al., 2020, Mostafa Araj-Khodaei et al., 2023). But berberine may be beneficial in the fight against Alzheimer’s as well. As it turns out, berberine may be able to combat neurodegenerative diseases by working with and protecting the infamous powerhouse of the cell: the mitochondria.

Mitochondria are present in virtually every cell in the human body. These double membraned organelles are responsible for generating ATP - our body’s main chemical energy source - from the foods we eat (Casanova et al., 2023). They are especially important for proper brain function. The trillions of synapses we have in our brains responsible for transmitting electrical and chemical signals are, unsurprisingly, areas of high energy demand. Therefore, having functioning mitochondria in these regions is essential for proper brain activity (Bustamante-Barrientos et al., 2023).

Mitochondrial dysregulation in the brain due to pathological conditions is often associated with an increase in reactive oxygen species and a loss of ATP production, which means a loss of energy (Guo et al., 2013). When scientists look at the brain cells of patients with Alzheimer’s disease, they find altered and damaged mitochondria (Wiśniewski et al., 1970), which subsequently are unable to produce the same energy output as healthy mitochondria (Europe PMC, 2016).

According to the Cleveland Clinic, Alzheimers is the most common form of dementia. It is a neurodegenerative disease that damages neurons in the brain, often resulting in symptoms such as memory loss, difficulty communicating, behavioral changes, and impaired motor function. Research predicts that in 2025, the number of people 65 and older afflicted with Alzheimer’s Disease in the United States will reach 7.1 million (Alzheimer’s Facts & Statistics, 2024).

Many of the symptoms associated with Alzheiemer’s are due to disruption in synaptic signaling (Zhao et al., 2019). Inspired by several animal studies showing that berberine could improve cognitive dysfunction, Zhao’s team wanted to see if berberine could protect against mitochondrial damage induced by amyloid beta plaques (a central biomarker of Alzheimer’s disease) in an in vitro Alzheimer’s study.

In their study, Zhao’s team pre-treated neural cell cultures with berberine, and then measured differences in cell viability, mitochondrial activity, and ATP production following an amyloid beta plaque insult (to stimulate the brain of a patient with Alzheimers). What they found was that cells that were pre-treated with berberine had a higher survival rate, recovered their mitochondrial membrane potential, and increased overall ATP production in a dose-dependent manner. While there have been studies that show the beneficial effects of berberine against neurodegenerative diseases due to its antioxidant activity (Cheng et al., 2022), this study was the first of its kind to evidence berberine as being beneficial due to its mitochondrial protective capabilities.

One important thing to note in Zhao’s findings is that it was an in vitro study, meaning these effects were observed under controlled conditions, and not in a clinical study or animal model. A unique characteristic of berberine is its ability to cross the blood brain barrier, which makes it particularly attractive as a neuroprotective therapeutic (Rondanelli et al., 2023). However, berberine taken orally has very poor absorption in the GI tract; less than 1% after a single dose (though daily supplementation can increase bodily concentration over time). To combat this low bioavailability, berberine phospholipids and berberine compounds have been manufactured which help increase its absorption (Rondanelli et al., 2023, Yang et al., 2024).

Staying in shape and maintaining a healthy brain are the hallmarks of happy and long-lived lives. And thanks to the recent studies on berberine’s pro-brain and pro-weight loss benefits, why wouldn’t you want to include it in your supplement rotation?

References

Alzheimer’s Facts & Statistics. (2024). Alzheimer’s San Diego. https://www.alzsd.org/resources/facts-stats/

Bustamante-Barrientos, F. A., Noymar Luque‐Campos, María Jesús Araya, Lara-Barba, E., Javiera De Solminihac, Pradenas, C., Molina, L., Yeimi Herrera-Luna, Yildy Utreras‐Mendoza, Elizondo‐Vega, R., Ana María Vega-Letter, & Luz‐Crawford, P. (2023).

Mitochondrial dysfunction in neurodegenerative disorders: Potential therapeutic application of mitochondrial transfer to central nervous system-residing cells. Journal of Translational Medicine, 21(1). https://doi.org/10.1186/s12967-023-04493-w

Casanova, A., Wevers, A., Navarro-Ledesma, S., & Pruimboom, L. (2023). Mitochondria: It is all about energy. Frontiers in Physiology, 14, 1114231. https://doi.org/10.3389/fphys.2023.1114231

Cheng, Z., Kang, C., Che, S., Su, J., Sun, Q., Ge, T., Guo, Y., Lv, J., Sun, Z., Yang, W., Li, B., Li, X., & Cui, R. (2022). Berberine: A Promising Treatment for Neurodegenerative Diseases. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.845591

Cleveland Clinic. (2022, December 10). Alzheimer’s disease. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/9164-alzheimers-disease

Europe PMC. (2016). Europe PMC. Europepmc.org. https://europepmc.org/article/med/6602819

Guo, C., Sun, L., Chen, X., & Zhang, D. (2013). Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regeneration Research, 8(21), 2003–2014. https://doi.org/10.3969/j.issn.1673-5374.2013.21.009

Li, M., Zhou, W., Dang, Y., Li, C., Ji, G., & Zhang, L. (2020). Berberine compounds improves hyperglycemia via microbiome mediated colonic TGR5-GLP pathway in db/db mice. Biomedicine & Pharmacotherapy, 132, 110953. https://doi.org/10.1016/j.biopha.2020.110953

Mostafa Araj-Khodaei, Mohammad Hossein Ayati, Akbar Azizi Zeinalhajlou, Tannaz Novinbahador, Yousefi, M., Mahdi Shiri, Ata Mahmoodpoor, Shamekh, A., Namazi, N., & Sarvin Sanaie. (2023). Berberine-induced glucagon-like peptide-1 and its mechanism for controlling type 2 diabetes mellitus: a comprehensive pathway review. Archives of Physiology and Biochemistry, 1–8. https://doi.org/10.1080/13813455.2023.2258559

Rondanelli, M., Gasparri, C., Petrangolini, G., Allegrini, P., Avenoso, D., Fazia, T., Bernardinelli, L., Peroni, G., Patelli, Z., Mansueto, F., Tartara, A., Cavioni, A., & Riva, A. (2023). Berberine phospholipid exerts a positive effect on the glycemic profile of overweight subjects with impaired fasting blood glucose (IFG): a randomized double-blind placebo-controlled clinical trial. European Review for Medical and Pharmacological Sciences, 27(14), 6718–6727. https://doi.org/10.26355/eurrev_202307_33142

Wiśniewski, H., Terry, R. D., & Hirano, A. (1970). Neurofibrillary pathology. Journal of Neuropathology and Experimental Neurology, 29(2), 163–176. https://pubmed.ncbi.nlm.nih.gov/5435819/

Yang, W.-L., Zhang, C.-Y., Ji, W.-Y., Zhao, L.-L., Yang, F.-Y., Zhang, L., & Cao, X. (2024). Berberine Metabolites Stimulate GLP-1 Secretion by Alleviating Oxidative Stress and Mitochondrial Dysfunction. the American Journal of Chinese Medicine, 1–22. https://doi.org/10.1142/s0192415x24500113

Zhao, C., Su, P., Lv, C., Guo, L., Cao, G., Qin, C., & Zhang, W. (2019). Berberine Alleviates Amyloid β-Induced Mitochondrial Dysfunction and Synaptic Loss. Oxidative Medicine and Cellular Longevity, 2019, 1–11. https://doi.org/10.1155/2019/7593608

Assessed and Endorsed by the MedReport Medical Review Board